Epigenomic Profiling Reveals DNA-Methylation Changes Associated with Major Psychosis

Epigenetics can be defined as changes in gene transcription through modulation of chromatin, which is NOT brought about by changes in the DNA sequence.Schrizophrenia(SZ) and bipolar disorder(BD) both conditions are known to be etiologically related and both conditions together are termed major psychosis. Different studies previously on major psychosis are based on interplay between genetics and epigenetics and observations led to the identification about the importance of epigenetic factors. Until now few studies on the role of DNA methylation in major psychosis are done but none have taken a whole genome wide epigenomic approach.In this paper author investigates the whole genomic approach using the DNA from frontal cortex, a region which has been etiologically implicated in psychiatric conditions. Samples from both SZ and BD patients were analysed with comparison to control samples.
Authors examined the DNA methylation with two complimentary approaches. They performed a microarray epigenomic scan using CpG island microarrays after the enrichment of unmethylated fraction of brain DNA by using restriction enzyme HpaII and McrBC.Secondly they performed a hypothesis driven analysis of DNA methylation for priori evidence of the role in the etiology of the major psychosis. They also did a CpG island microarray to investigate the differences in the germline DNA in BD patients. Numerous loci including glutamatergic and GABAergic neurotransmission, brain development and other processes linked to disease are analysed. Methylome network analysis revealed the decreased epigenetic modularity in the affected individuals.Hence considerable epigenetic changes were found as evidence for the epigenetic relation to etiology of major psychosis. As the epigenetic changes are reversible this can lead to epigenetic treatment of the psychiatric conditions. Epigenetics is also found to have role in memory, hippocamal development and many other functions of the brain and hence the study of epigenetics in the psychiatry field might uncover many unknown facts of brain chemistry.

Raja Lella
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